RNA tumor viruses are capable of inducing tumors in their natural hosts and of transforming cells in culture. The overall objective of our research effort is to understand the control of integrated avian sarcoma virus (ASV) gene expression in a number of different ASV-infected transformed and revertant mammalian cell lines. To this end we are determining the location, specificity and stability of the ASV integration site(s) on the mammalian host cell genome. We have found that there are a large number of sites on the mammalian cell genome into which the viral DNA can be inserted. Using specific cDNA probes and probes generated by DNA cloning techniques, we will attempt to determine if these host cell "integration sites" have a common feature that is required for the integration of the viral genome. We are also examining the stability of the integrated ASV genome to determine if the ASV genome can be excised and re-inserted into another cellular DNA site during growth of these transformed cells in culture. The third objective of our work is to determine the possible relationship between the host cell integration site and the level of viral gene expression. We are currently examining the arrangement of integrated ASV sequences in a series of morphological revertants of ASV transformed mammalian cells. We are now examining the cellular sequences adjacent to the integrated provirus in these revertants to see if a modification of these neighboring cellular sequences is responsible for the lack of expression of the transformed phenotype. These studies may shed some light on the control of ASV gene expression in ASV-infected mammalian cells and may enhance our understanding of viral-mediated transformation.